Cell fusion is a fundamental biological event that is essential for a variety of developmental and homeostatic processes. Although intracellular membrane fusion during organelle trafficking is well understood, less is known about cell-cell fusion mediating sperm-oocyte, myoblast-myoblast, and macrophage-macrophage fusion. See, Vignery (2000) Int. J. Exp. Pathol. 81:291-304.
With respect to macrophages, these cells can fuse with themselves (i.e., homotypic fusion) in tissue to form giant cells, which are involved in chronic inflammatory diseases. See, MacLauchlan et al. (2009) J. Leukoc. Biol. 85:617-626; and Vignery (2000), supra. In addition, macrophages can fuse with themselves in bone to form osteoclasts, which mediate bone resorption. More recently, it is believed that macrophages can fuse with somatic or cancer cells (i.e., heterotypic fusion). See, Vignery (2005) Trends Cell Biol. 15:188-193.
Unfortunately, the mechanism(s) by which macrophages fuse with themselves and other cells remain largely uncharacterized. See, MacLauchlan et al. (2009), supra; and Vignery (2005), supra. Understanding this process can help to modulate macrophage function and also limit the damage caused in inflammatory and infectious diseases when these cells fuse in an inappropriate or unregulated manner. For the foregoing reasons, there is a need for compositions and methods for inhibiting macrophage fusion.
Osteoclasts are formed by the fusion of cells of the monocyte-macrophage cell line. An osteoclast is a large cell that is characterized by multiple nuclei and a high concentration of vesicles and vacuoles. Osteoclasts form a specialized cell membrane at a site of active bone resorption which facilitates removal of the bony matrix. Such mechanism results in osteoporosis or osteopenia (having a bone mineral density that is lower than normal but not low enough to be classified as osteoporosis). Rheumatoid arthritis is often complicated by generalized osteopenia due to increased bone resorption by osteoclasts. Thus, there is also a need for compositions and methods for modulating, particularly inhibiting, osteoclast differentiation and function.